Pharmacology Biochemistry and Behavior最新文献

{"title":"Different protocols of REM sleep deprivation led to controversial effects on OCD- and anxiety-like behaviors and locomotor activity in fear conditioning male and female rats with respect to BDNF expression level","authors":"Masoumeh Payamani ,&nbsp;Seyedeh-Tabassom Abdollahi-Keyvani ,&nbsp;Mandana Sajjadi ,&nbsp;Shahin Akhondzadeh ,&nbsp;Reihane Javid ,&nbsp;Reihaneh Nakhaei-Zadeh ,&nbsp;Marzieh Jalalian-Javadpour ,&nbsp;Salar Vaseghi","doi":"10.1016/j.pbb.2025.174027","DOIUrl":"10.1016/j.pbb.2025.174027","url":null,"abstract":"<div><div>Specific protocols of rapid-eye movement (REM) sleep deprivation (SD) may lead to behavioral phenotypes considered as obsessive-compulsive disorder (OCD)-like behavior and hyperactivity (mania-like behavior). The present study aimed to assess the effects of REM SD on both sexes of control and fear conditioning (FC) rats. REM SD was induced for 1 or 2 or 3 weeks (6 h/d). Freezing, locomotor activity, anxiety-like behavior, grooming and burying marbles (OCD-like behaviors), and brain-derived neurotrophic factor (BDNF) in the hippocampus were evaluated. The results showed 1w REM SD decreased freezing in females, while 2w and 3w REM SD decreased freezing in both sexes. Locomotor activity in 2w REM SD males was increased, while was decreased in 3w group. In females, both 2w and 3w REM SD increased locomotion. REM SD in both sexes increased locomotion in FC rats. All REM SD protocols decreased anxiety in both sexes of FC rats. REM SD in control and FC rats led to OCD-like behaviors. All REM SD protocols decreased BDNF in both sexes, while 3w slightly increased it, suggesting a compensatory mechanism over time. 2w and 3w REM SD increased BDNF in FC rats in both sexes. Pearson correlation test also showed that changes in BDNF levels may be related to some behavioral changes only in females. In conclusion, for the first time, the present study showed sex differences in the effects of REM SD on behavioral functions in control and FC rats, and in the relationship between BDNF levels and behavioral changes.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174027"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dosage-dependent effects of cevimeline in preventing clozapine-induced dyslipidaemia in female rats","authors":"Jiamei Lian ,&nbsp;Bo Pan ,&nbsp;Chao Deng","doi":"10.1016/j.pbb.2025.174017","DOIUrl":"10.1016/j.pbb.2025.174017","url":null,"abstract":"<div><div>Clozapine is the most effective second-generation antipsychotic drug, especially for the therapy of treatment-resistant schizophrenia. However, it is associated with metabolic side-effects. Clozapine has a high antagonistic affinity to muscarinic M3 receptors, which has been reported to play a significant role in these side-effects. This study aimed to investigate whether co-administration of cevimeline (an M3 receptor agonist) could prevent the metabolic disorders induced by clozapine. Female Sprague Dawley rats were treated orally with clozapine (20 mg/kg, 3 times daily) and/or cevimeline at three dosages (3, 6, 9 mg/kg, 3 times daily), or a vehicle for two weeks. Body weight gain, food/water intake, and temperature were recorded. Open field tests were performed to assess motor activity. Clozapine only treatment significantly decreased body weight gain, feeding efficiency, perirenal, periovary, inguinal, total white fat mass, and NEFA levels. The reduction in body weight gain and feeding efficiency caused by clozapine was partially reversed by co-treatment with 3 or 6 mg/kg cevimeline. Clozapine also significantly increased the liver mass, LDL, and HDL level, which were reversed by the co-treatment with cevimeline at all tested dosages. These results support further clinical trials to evaluate cevimeline's potential in controlling clozapine-induced dyslipidemia.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174017"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reward contamination in restrictive anorexia nervosa: A meta-analysis of functional MRI studies","authors":"Charlotte S. Rye ,&nbsp;Felippe E. Amorim ,&nbsp;Laetitia H.E. Ward ,&nbsp;Amy L. Milton","doi":"10.1016/j.pbb.2025.174031","DOIUrl":"10.1016/j.pbb.2025.174031","url":null,"abstract":"<div><div>Individuals with anorexia nervosa (AN) are typically anhedonic, leading to the suggestion that intrinsic disturbances of reward processing may represent a trait marker of the disorder. Previous studies have used task-based functional magnetic resonance imaging (fMRI) to investigate reward-related brain activity in AN and reported altered activation in the prefrontal cortex, dorsal posterior cingulate cortex, and rostral anterior cingulate cortex. However, likely due to the varied paradigms and methodologies used, as well as the heterogeneity in sample characteristics, results have proved inconsistent. To determine whether AN patients with the restrictive subtype (AN-r) show different reward-induced activation patterns to matched healthy controls (HCs) at different illness stages, we conducted a meta-analysis of 19 task-based fMRI studies of reward-processing. Using the seed-based differential mapping (SDM) technique, we found differences in reward-related brain activity between AN-r and HCs. Moreover, different brain regions showed differential activation across illness stages, with the direction and magnitude of effects dependent on specific task stimuli. These findings suggest that those with AN-r show distorted reward processing as a consequence of reward contamination and alterations in valence assignment to reward stimuli. In weight-recovered AN-r patients, differences to HCs persisted but were limited to regions known to exhibit significant atrophy in AN-r, indicating that altered reward processing is associated with anorectic undernutrition. These findings have implications for developing pharmacological treatments to aid psychological recovery in AN-r.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174031"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous cocaine and ethanol self-administration promotes a sex-dimorphic pattern in drug-seeking behaviour and alters plasma amino acid profile related to glutamate homeostasis in young adult rats","authors":"Lucía Garrido-Matilla,&nbsp;Alberto Marcos,&nbsp;Natalia Puig-Martínez,&nbsp;Emilio Ambrosio","doi":"10.1016/j.pbb.2025.173988","DOIUrl":"10.1016/j.pbb.2025.173988","url":null,"abstract":"<div><div>The concurrent use of cocaine and alcohol is highly prevalent in Western countries and carries a substantial risk of relapse in recovering process. Craving, characterized as a strong desire for consuming drugs, is a core feature of cocaine and ethanol use disorders and presents a significant challenge to maintaining abstinence and preventing relapse. The primary objective of this study was to explore the behavioural patterns associated with the incubation of drug-seeking for a cocaine-ethanol combination and, secondarily, to examine the plasma amino acid profile that might be associated with this combination. To achieve this, we employed an extended-access intravenous self-administration model over 10 sessions with both substances, followed by withdrawal periods of 2 and 30 days in young adult rats in both sexes. After the subsequent drug-seeking test, changes in plasma amino acid concentrations were examined. Cocaine and ethanol co-administration resulted in a lower consumption rate among rats compared to those consuming cocaine alone. However, both groups exhibited incubation of drug-seeking behaviour. Sex differences were observed in self-administration patterns and in the incubation of drug-seeking behaviour. Notably, after 30 days of withdrawal, alterations were detected in plasma levels of several amino acids, including glutamine, glycine, serine, threonine, and glutamate, which are associated with glutamate homeostasis. This study aims to contribute to our understanding of potential changes in the plasma amino acid profile in cocaine users who also consume ethanol, particularly during abstinence and craving incubation.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 173988"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agomelatine with cognitive behavioral therapy reduces insomnia severity index and subjective units of distress scores than initial-dose clonazepam in moderate to severe insomnia patients: A quasi-experimental study","authors":"Kousalya Prabahar ,&nbsp;Abinaya Ravikumar ,&nbsp;Anu Priya Jeyabalan ,&nbsp;Bharath Ravi ,&nbsp;Chandini Ravikumar ,&nbsp;Nithishadevi PannirukaiSelvan ,&nbsp;Saleh F. Alqifari ,&nbsp;Varadharajan Sivaraman ,&nbsp;Natarajan Shanmugasundaram ,&nbsp;Karthik Sankar","doi":"10.1016/j.pbb.2025.174003","DOIUrl":"10.1016/j.pbb.2025.174003","url":null,"abstract":"<div><h3>Background</h3><div>Insomnia can be caused by various factors including lack of sleep, stress, sadness, hormonal changes, excessive caffeine, anxiety, mental health disorders, and medications. Treatments include finding the cause, improving sleep patterns, using behavioral therapy, and taking sleeping pills in most cases. However, the drugs often cause worse side effects than insomnia. This study compared the efficacy of initial agomelatine and clonazepam doses with cognitive behavioral therapy for insomnia (CBT-i) in moderate to severe insomnia patients.</div></div><div><h3>Methods</h3><div>This quasi-experiment study involved 230 moderate to severe insomnia patients with group A as clonazepam 0.25 mg and B as agomelatine 25 mg. CBT-i was received by both of the groups and the Insomnia Severity Index (ISI), Subjective Units of Distress Scale (SUDS) score, medication adherence, and Adverse Drug Reactions (ADRs) were followed for up to 24 weeks.</div></div><div><h3>Results</h3><div>In the comparative analysis between and within groups, group B exhibited a significant reduction in ISI (<em>p</em> = 0.001) and SUDS (p = 0.001) scores at week 24 compared to group A. Overall, both groups demonstrated improved adherence. However, 12 patients in group A and 10 in group B experienced ADR, which included drowsiness, hypersalivation, diarrhea, maculopapular rash, and myotoxicity. The clonazepam-treated group showed reduced efficacy from week 12 onwards in the ISI and from week 16 in the SUDS median score, which was not observed in the agomelatine group.</div></div><div><h3>Conclusion</h3><div>The initial dose of agomelatine with CBT-i has a better impact on improving moderate to severe insomnia than the initial dose of clonazepam with CBT-i.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174003"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychostimulant induced behavioral sensitization: The contribution of drug stimuli to context and Pavlovian conditioned stimuli","authors":"Robert J. Carey","doi":"10.1016/j.pbb.2025.174011","DOIUrl":"10.1016/j.pbb.2025.174011","url":null,"abstract":"<div><div>The drug induced enhancement of behavioral stimulation effects with repeated drug treatments is frequently context specific implicating associative processes. Attempts to label these effects as Pavlovian conditioned drug responses have generally been dismissed as it has frequently been demonstrated that the test environment cues alone are insufficient to elicit the sensitized drug response. In this paper evidence will be presented showing that the sensitized drug response can in fact be elicited by test environment cues in a non-drug test. The key reason test environment cues alone are an inadequate conditioned stimulus to elicit the sensitized drug response with commonly used behavioral sensitization protocols is because drug stimulus cues of the drug used to induce behavioral sensitization are conflated with the test environment cues so that the conditioned stimulus has been transformed into a compound conditioned stimulus comprised of the test environment cues co-mingled with the drug stimulus cues In this paper we will present evidence that shows that modifications in the drug testing protocol such as placement of the subject into the test environment immediately after drug administration so that the test environment cues precede the onset of the drug response creates the opportunity for a Pavlovian test environment/drug response association. Also, the use of posttest drug administration can enable the test environment stimulus trace to be selectively paired with the drug response and acquire conditioned stimulus properties and become sufficient to elicit the sensitized behavioral drug response. From a Pavlovian conditioning perspective, repeated pairing of the drug with the test environment enables the conditioned drug response test response to add to the unconditioned drug response to generate a behavioral sensitization effect. Critically, the context needs to be recognized as a conditioned stimulus composite comprised of the test environment cues coupled with the drug generated stimulus cues.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174011"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoamine receptors targeted by methamphetamine differentially modulate basal and fentanyl-depressed respiration in mice","authors":"Harrison J. Elder ,&nbsp;D. Matthew Walentiny ,&nbsp;Patrick M. Beardsley","doi":"10.1016/j.pbb.2025.174004","DOIUrl":"10.1016/j.pbb.2025.174004","url":null,"abstract":"<div><h3>Rationale</h3><div>Fentanyl remains the primary cause of fatal overdoses, and its co-use with methamphetamine is a growing concern. Our lab previously demonstrated that racemic methamphetamine could have either respiratory stimulant or depressant effects depending on dose and separately determined by its enantiomers, dextromethamphetamine, and levomethamphetamine, respectively. Enantiomeric separation of methamphetamine's stimulant and depressant effects indicates that differences in their pharmacology might be exploited to develop novel respiratory stimulants. It is presently unknown which of methamphetamine's monoamine receptor mechanisms mediate these respiratory effects. Thus, systematic evaluation of monoamine receptor-selective agents may identify treatment targets for OIRD.</div></div><div><h3>Methods</h3><div>Six selective agonists at monoamine receptors involved in methamphetamine's activity [phenylephrine (PNE; α₁), clonidine (CLON; α₂), SKF-82958 (SKF; D₁), quinpirole (QPR; D₂-like), 8-OH-DPAT (8-OH; 5HT_1A), and DOI (5HT₂)] were tested in adult male mice to determine their effects on basal and fentanyl-depressed minute volume (MVb; i.e., respiratory frequency x tidal volume) using whole-body plethysmography. Agonists were initially tested at three behaviorally active doses for their effects on basal MVb. Agonists that stimulated respiration or did not decrease respiration were then tested in combination with fentanyl.</div></div><div><h3>Results</h3><div>The α₁ and D₁ agonists PNE and SKF dose-dependently increased basal MVb while the α₂ and D₂-like agonists CLON and QPR depressed basal MVb. Neither serotonin receptor agonist significantly altered basal MVb. Under fentanyl-depressed conditions, SKF produced transient but significant increases in MVb, while PNE more persistently elevated it. Interestingly, DOI transiently elevated depressed MVb, while 8-OH further exacerbated OIRD.</div></div><div><h3>Conclusions</h3><div>Selective activation of monoamine receptors alters basal respiration and OIRD, with D₁ and α₁ receptors representing potential targets as respiratory stimulants, whereas α₂, D₂-like, and 5HT_1A receptors may mediate the exacerbation of OIRD by methamphetamine.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174004"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review and meta-analysis of weight gain and metabolic changes in children and adolescents using second-generation antipsychotics","authors":"Suzana Figueiredo Collares ,&nbsp;Antônio Márcio de Ávila Júnior ,&nbsp;Tamires Coelho Martins ,&nbsp;Victhor Hugo Martins Rezende ,&nbsp;Marco Aurélio Romano-Silva ,&nbsp;Renata Maria Silva Santos ,&nbsp;Débora Marques de Miranda","doi":"10.1016/j.pbb.2025.174012","DOIUrl":"10.1016/j.pbb.2025.174012","url":null,"abstract":"<div><div>The use of second-generation antipsychotics in children and adolescents has significantly increased in recent decades, raising concerns about side effects such as weight gain, dyslipidemia, and insulin resistance. These effects are concerning during development, as they may predispose individuals to adult obesity and metabolic complications. Therefore, the aim of this review is to update the evidence on associations between the use of these medications, weight gain, BMI changes, and major metabolic alterations in children and adolescents. This review was conducted following the PRISMA protocol and registered in PROSPERO under the number: CRD42024549448. The search was carried out in March 2024 using the terms “child,” “adolescent,” “weight gain,” “metabolism disorders,” and “antipsychotics,” combined with the AND operator in the MEDLINE, Scopus, Cochrane, and PubMed databases. The main findings of this review included weight gain, increased BMI, and metabolic alterations, such as insulin resistance and increased abdominal circumference. The meta-analysis highlighted a positive association between one of the investigated second-generation antipsychotics and weight gain. Therefore, prescriptions may be accompanied by strict guidelines for nutritional monitoring and metabolic control interventions.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174012"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats","authors":"Ariana C. Brice-Tutt ,&nbsp;Niall P. Murphy ,&nbsp;Barry Setlow ,&nbsp;Alexandria S. Senetra ,&nbsp;Wendi Malphurs ,&nbsp;Robert M. Caudle ,&nbsp;Adriaan W. Bruijnzeel ,&nbsp;Marcelo Febo ,&nbsp;Abhisheak Sharma ,&nbsp;John K. Neubert","doi":"10.1016/j.pbb.2025.173968","DOIUrl":"10.1016/j.pbb.2025.173968","url":null,"abstract":"<div><div>Previous studies have driven the notion that the cannabis constituent cannabidiol could be an effective adjunct to opioid administration for managing pain. Most of these studies have used experimental rodents with routes of administration, such as subcutaneous and intraperitoneal, that do not correspond with the routes used in clinical practice. In response to this, we tested the ability of cannabidiol co-administration to augment opioid analgesia via the more clinically-relevant oral route of administration. To this end, male and female rats were orally gavaged with cannabidiol (25 mg/kg), oxycodone (1.4 mg/kg), or a combination of both, after which they were tested in an operant thermal orofacial pain assay in which they voluntarily exposed their faces to cutaneous thermal pain to receive a palatable reward. All three drug conditions produced analgesic effects of varying degrees, being most profound in the combination group where a statistically significant enhancement over oxycodone-induced analgesia alone was evident. Additionally, oxycodone administration decreased lick frequencies – a measure of motor coordination of rhythmic movements - which too was magnified by co-administration of cannabidiol. Together these studies provide further support of an ability of cannabidiol to augment opioid effects, particularly analgesia, when administered by a route relevant to human pain management. As such, they encourage the notion that cannabidiol could find utility as an opioid-sparing approach to treating pain.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"250 ","pages":"Article 173968"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coadministration of scopolamine and mGlu2 receptor negative allosteric modulator VU6001966 as a potential therapeutic approach for depression: Rat frontal cortex neurochemistry and behavior","authors":"Yana Babii ,&nbsp;Agnieszka Pałucha-Poniewiera ,&nbsp;Krystyna Gołembiowska ,&nbsp;Agnieszka Bysiek ,&nbsp;Izabela Szpręgiel ,&nbsp;Andrzej Pilc","doi":"10.1016/j.pbb.2025.173996","DOIUrl":"10.1016/j.pbb.2025.173996","url":null,"abstract":"<div><div>Clinical studies provide evidence that scopolamine, a nonselective antagonist of muscarinic cholinergic receptors, exerts rapid and prolonged antidepressant effects. However, its use as a psychiatric drug has been limited due to its significant adverse effects. A therapeutic option that could help reduce the adverse effects of scopolamine is its coadministration at lower doses with other substances with similar antidepressant properties. To address this issue, we have investigated the effect of a single acute coadministration of scopolamine and a negative allosteric modulator of the mGlu2 receptor VU6001966 on rat behavior using a forced swim test (FST) and locomotor activity test. The effect of given compounds on the extracellular levels of neurotransmitters in the rat frontal cortex (FCX) was examined using microdialysis in freely moving rats. Both scopolamine and VU6001966 induced dose-dependent antidepressant-like effects in the FST test without affecting locomotor activity. Furthermore, VU6001966 enhanced extracellular dopamine and serotonin levels while lowering glutamate, without affecting GABA level. Both scopolamine alone or in combination with VU6001966 increased dopamine, serotonin, and glutamate levels in the FCX, without affecting GABA levels. Our results suggest that coadministration of scopolamine with mGlu2 NAM might be a promising alternative to using scopolamine alone in depression therapy, potentially allowing for a lower therapeutically effective dose. The common mechanism underlying the observed behavioral effects of the tested drugs may be associated with the modulation of the serotoninergic, glutamatergic, and dopaminergic systems.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"250 ","pages":"Article 173996"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}